Each minute of delay cut survival chance by 5%

Action Points

Note that this observational study found that, among children with non-shockable in-hospital cardiac arrest, earlier epinephrine administration was associated with better overall survival.

Be aware that no randomized trial of epinephrine administration exists, but the weight of evidence makes such a study unethical to perform.

Timely use of epinephrine was associated with increased survival among hospitalized children in nonshockable rhythm cardiac arrest, researchers reported.

Delayed adrenaline administration was associated with worse survival and other outcomes in the pediatric in-hospital cardiac arrest setting, the analysis of data from the American Heart Association's "Get With the Guidelines-Resuscitation" registry (GWTG-R) confirmed.

Multivariable analysis revealed that longer time to epinephrine administration was associated with lower risk of survival to discharge (multivariable-adjusted risk ratio per minute delay, 0.95, 95% CI 0.93 to 0.98), according to Lars W. Anderson, MD, of Beth Israel Deaconess Medical Center, Boston, and colleagues writing in the August 25 issue of the Journal of the American Medical Association.

Children in nonshockable cardiac arrest who did not receive epinephrine within 5 minutes of the event had a lower likelihood of survival than children who did (21% survival versus 33.1%; multiple adjusted RR 0.75, 95% CI 0.60 to 0.93; P=0.01).

Delays in epinephrine administration were also associated with worse outcomes on secondary measures, including return of spontaneous circulation (ROSC), survival at 24 hours, and neurological impairment.

"These associations remained when accounting for multiple predetermined potentially confounding patient, event, and hospital characteristics and in multiple difference sensitivity analyses," the researchers wrote. "Although the observational design precludes ascertainment of causality, the strong association with outcomes suggests that early epinephrine may be beneficial in pediatric cardiac arrest."

As many as 16,000 children in the U.S. suffer cardiac arrest each year -- mostly in a hospital setting -- and their survival rate is poor.

"An initial rhythm of pulseless electrical activity or asystole (i.e., a nonshockable rhythm) is most common and carries a significant mortality, with 25% to 40% of patients surviving to hospital discharge," Anderson and colleagues wrote.

Delayed epinephrine administration has been associated with worse outcomes in the adult in-hospital nonshockable cardiac arrest setting, but the impact of delayed administration in the pediatric setting has not been known.

"To our knowledge, no randomized trial comparing epinephrine with placebo has been conducted in this population, and the ethics of such a trial may currently be questionable," the researchers wrote.

The AHA's 2010 pediatric advanced life support (PALS) guidelines recommend giving epinephrine at 0.01 mg/kg (maximum, 1 mg) as soon as vascular or intraosseous access is obtained, followed by repeat administration every 3 to 5 minutes for patients with nonshockable rhythm.

The analysis of GWTG-R data identified 1,558 pediatric cardiac arrest patients, with a median age of 9 months (interquartile range 13 days to 5 years).

Slightly less than one-third of these patients (31.3%) survived to hospital discharge. The median time to first epinephrine dose was 1 minute (IQR 0-4; range 0-20; mean 2.6 minutes). Median time to chest compression was 0 minutes (IQR 0-0).

A total of 993 (63.7%) patients had return of spontaneous circulation, and 745 (47.8%) were alive 24 hours after the event. Just 217 (15.6%) had a documented favorable neurological outcome at hospital discharge.

In an editorial published with the study, Robert Tasker, MD, and Adrienne Randolph, MD, of Boston Children's Hospital, wrote that the study confirms the poor prognosis of children who suffer nonshockable in-hospital cardiac arrest, noting that less than a third of children survived to hospital discharge and fewer than 1 in 5 survived with favorable neurocognitive outcomes.

"Given there will never be a randomized clinical trial and that epinephrine is listed in the PALS guidelines as the next step after CPR for nonshockable rhythms, these new data provide fairly strong evidence that following the guidelines with regards to epinephrine dosing and timing is best practice, with this study likely providing an AHA Class I strength of recommendation," they wrote.

They added that the new findings support the current recommendations, but questions remain about the optimal timing of adrenaline administration.

"It is not known if epinephrine should be given within 2 minutes, as a good number of patients did not receive the drug at all and had ROSC in that time," they wrote.

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